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What is the definition of bipolar disorder?
a disorder of mood or affect defined by the presence of at least 1 manic episode at some point in the pts life
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What is the definition of mania?
an abnormally and persistently elevated, expansive, or irritable mood that lasts at least 1 wk and causes marked impairment in functioning
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What is the definition of hypomania?
an abnormally and persistently, elevated, expanxive, or irritable mood that lasts at least 4d but does not cause marked impairment in functioning
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What is the definition of mixed episode?
criteria for both a major depressive episode and manic episode occur nearly every day for at least 1 wk
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What is the definition of bipolar Type I?
manic episode +/- major depressive or mixed episode
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What is the definition of bipolar Type II?
major depressive episode +/- hypomanic episode
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What is the definition of dysthymic disorder?
chronic subsyndromal depressive episodes
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What is the definition of cyclothymic disorder?
chronic fluctuations b/w subsyndromal depressive and hypomanic episodes (2y for adults; 1y for children and adolescents)
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What is the definition of bipolar disorder not otherwise specified?
mood states do not meet criteria for any specific bipolar disorder
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What is the definition of rapid cycling?
4 major depressive or manic episodes (manic, mixed, or hypomanic) in 12mo
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When does bipolar usually show up?
- usually b/w 15 and 30
- average age = 21
- after 60 is rare and usually medically induced
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What type of bipolar episode is usually first for women?
major depressive
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What type of bipolar episode is usually first for men?
mania
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Which sex is more likely to have mixed, depressive, or rapid cycling?
females
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What types of bipolar is CBZ useful for ?
mixed states, rapid cycling....but second line due to poorly tolerated SE and DI
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What is the most common serum concentration of CBZ?
6-12 Mcg/ml
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What are the advantages of CBZ?
- effective for broad spectrum of bipolar pts
- ER capsules available
- relatively cheap for standard dosage forms (cheaper than Depakote)
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What are the disadvantages of CBZ?
- CNS SE not well tolerated (but can develop tolerance and dose-dependent)
- rashes - rarely severe
- blood dyscrasias
- many DI
- teratogenic
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What are some DI of CBZ?
- Fluoxetine
- Fluvoxamine
- VPA
- antibiotics (esp. erythro)
- many antipsychotics
- warfarin
- ORAL CONTRACEPTIVES
Induces it's own metabolism so check levels after couple wks
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Carbamazepine
Decreased neurotransmitter turnover, increased substance P, Na+ channel blockade, et al
- diplopia
- blurred vision
- nystagmus
- ataxia
- dizziness
- HA
- sedation
- rashes
- leukopenia
- thrombocytopenia
- anemia
- aplastic anemia - very rare
- hepatitis - very rare
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What antipsychotics are approved for bipolar acute mania?
- olanzapine
- risperidone
- quetiapine
- aripiprazole
- ziprasidone
- asenapine
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Which antipsychotics are good for mixed states?
- aripiprazole
- risperidone
- olanzapine
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Which antipsychotic is approved for treatment of bipolar depression?
quetiapine (the only first line alternative for this)
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Which antipsychotic is approved for maintenance treatment of bipolar?
quetiapine
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Which antipsychotic is associated with frequent akathisia?
aripiprazole
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What are the concerns of using FGA's for adjunct treatment of bipolar?
tardive dyskinesia (greater than in SCZ)
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What are the advantages of antipsychotics in bipolar disorder?
- FGA's have fast onset on some behaviors (within a week)
- helpful in partial responders and manic pts with psychotic features
- some available as immediate release injectables
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Which antipsychotics are available as immediate release injectables?
olanzapine, ziprasidone, aripiprazole
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What are the disadvantages of antipsychotics in treatment of bipolar disorder?
- bipolar pts at higher risk of FGA SE than other pts (esp. TD)
- some SGAs are VERY expensive
- use lowest effective doses to avoid SE
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Lamotrigine
anti-convulsant ("novel mood stabilizer")
- For maintenance of stabilized patients only
- 1st line for bipolar depression
- Nausea
- anorexia
- sedation
- tremor
- ataxia
- dizziness
- HA
- blurred vision
- insomnia
- aseptic meningitis - rare
- rash (Stevens-Johnson) - tritrate SLOWLY and do not use with VPA
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Oxcarbazepine
anti-convulsant ("novel mood stabilizer")
fewer DI and better tolerance than CBZ
- sedation
- rash (benign)
- HA
- dizziness
- NV
- hyponatremia - mainly in elderly
induces metabolism of oral contraceptives
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Tamoxifen
Protein Kinase C inhibitor ("novel mood stabilizer")
experimental ONLY for BD acute mania
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What does Switch mean in bipolar depression?
time from depression to mania may be shortened by antidepressants
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What is first line therapy for bipolar depression?
- Li
- quetiapine
- lamotrigine
- VPA
- any of the above + antidepressant (esp. SSRI or bupropion)
- AVOID antidepressant monotherapy - combine with a mood stabilizer or AAP
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What is second line treatment for bipolar depression?
- quetiapine + CBZ or Li
- add CBZ to existing regimen
- Li or VPA + lamotrigine
- olanzapine + fluoxetine
- Li or VPA + olanzapine
AVOID venlafaxine, it seems to have higher risk of Switch than other ADs
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Quetiapine is approved for what type of depression?
bipolar depression ONLY (not major depression)
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What drugs are used for bipolar disorder?
- Li
- VPA
- CBZ
- Lamotrigine
- Oxcarazepine
- AP
- AD
- BZD
- CCB (for HTN comorbidity)
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How long does it take to see a response from mood stabilizers in bipolar pts?
1-2 wks
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What is the efficacy of mood stabilizers in bipolar pts?
- better for mania than depression
- better for acute episodes than for prophylaxis
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Why should Li, VPA, and CBZ be avoided during pregnancy?
they are all known teratogens
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Which drug is the DOC for classic, euphoric mania?
Li, but 20-30% may not respond to tx
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What is the problem with taking pts off of Li or pts who are intermittently compliant?
10% may experience withdrawal-induced refractoriness, but this is RARE
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Why is Li the "kineticist's dreamdrug"?
- 100% absorption
- 0 PPB
- 0 metabolism
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How is Li excreted?
- 96% in urine
- 4% in sweat
- 80% is reabsorbed at the proximal tubule
- Cl = 0.2 x CrCl
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What are the target plasma concentrations of Li?
- 0.8-1.2 meq/L for acute mania
- 0.6-1.0 meq/L for maintenance tx
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When must a sample be drawn to ensure Li has reached steady state?
4-5d after initiation of tx and 12h after last dose
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What are the advantages of Li?
- yrs of experience
- best mood stabilizer for manic or depressive (lamotrigine or quetiapine?) episodes
- cheap
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What are the disadvantages of Li?
- toxic in OD
- teratogenic
- requires therapeutic monitoring
- many DI
- many SE
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What are the SE of Li?
- sedation
- polyuria
- polydipsia (thirst)
- NVD
- anorexia
- wt gain
- fine tremor
- edema
- cystic acne
- leukocytosis
- t-wave inversion resembling hypokalemia
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What are the acute toxic effects of Li?
- persistent vomiting/diarrhea
- muscle weakness
- coarse tremor
- ataxia
- dysarthria
- irritability or agitation
- lethargy
- somnolence
- seizures
- coma
- death
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What are the chronic toxic effects of Li?
- goitrogenic hypothyroidism (levothyroxin - but reversibility is questionable)
- Renal tubular necrosis (stop Li)
- diabetes insipidus syndrome (stop Li)
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If Li levels are 0.4-0.8 and pt has insomnia, what should be done?
increase dose, they are not controlled (Li is sedating)
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What labs should be drawn prior to Li institution?
- BUN
- Scr
- urinalysis
- serum electrolytes
- thyroid fx
- ECG
- CBC w/ differential
- pregnancy test
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What DI should you worry about with Li?
- NSAIDs - decrease clearance of Li (ASA and sulindac ok)
- diuretics - increase clearance of Li (thiazides, not loops)
- ACEI and ARBs increase Li concentrations
- significant changes in salt intake
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What is first line tx for bipolar according to CANMAT?
- Li
- VPA
- Aripiprazole
- Risperidone
- Ziprasidone
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What are the advantages of VPA (Depakote)?
- well tolerated
- efficacy includes rapid cyclers, mixed states and presence of EEG abnormalities
- safer than Li
- DR form is generic
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What are the disadvantages of VPA (Depakote)?
- expensive (except DR)
- not as effective for depressive episodes
- hepatotoxic (all were in kids on multiple antiepileptics)
- teratogenic
- many SE
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What are the SE of VPA (Depakote)?
- hyperammonemia (usually benign - monitor for hepatic and CNS toxicity)
- wt gain
- increased appetite or anorexia
- NVD (use enteric coated, give w/food, or add H2 blocker)
- cramping
- ataxia (modify dose)
- drowsiness/sedation (modify dose
- tremor (modify dose or add BBL)
- alopecia (hair loss - tolerance possible, reversible; try Zn and Se supplements)
- menstrual irregularities
- thrombocytopenia (modify dose)
- elevated liver enzymes (usually benign, educate pt on signs of liver failure, modify dose, d/c if >2x normal)
- hepatotoxicity (rare - d/c drug)
- pancreatitis (rare - d/c drug)
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